N,N'-Dimethylethylenediamine → (R)-3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3,5-difluorophenyl}-4-ethyloxazolidin-2-one

HRID 1804222노트

반응식

HRID 1804222 반응식
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[CH:19][N:18]=3)[CH2:13][CH2:12]2)=[O:10])=[C:4]([F:25])[CH:3]=1.[CH2:26]([C@@H:28]1[CH2:32][O:31][C:30](=[O:33])[NH:29]1)[CH3:27].C(=O)([O-])[O-].[K+].[K+].CNCCNC.[Cl-].[NH4+]>[Cu]I.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH3:23][C:22]1[C:17]([N:14]2[CH2:15][CH2:16][N:11]([C:9]([C:5]3[C:6]([F:8])=[CH:7][C:2]([N:29]4[C@H:28]([CH2:26][CH3:27])[CH2:32][O:31][C:30]4=[O:33])=[CH:3][C:4]=3[F:25])=[O:10])[CH2:12][CH2:13]2)=[N:18][CH:19]=[C:20]([CH3:24])[CH:21]=1

참가 물질

9

반응물 5

HCID 8070N,N'-Dimethylethylenediamine2회HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 641503(4R)-4-ethyl-1,3-oxazolidin-2-oneHCID 58484761(4-Bromo-2,6-difluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone

생성물 1

HCID 67380886(R)-3-{4-[4-(3,5-dimethylpyridin-2-yl)piperazine-1-carbonyl]-3,5-difluorophenyl}-4-ethyloxazolidin-2-one수율 62.8%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매2회HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

To a mixture of (4-bromo-2,6-difluorophenyl)[4-(3,5-dimethylpyridin-2-yl)piperazin-1-yl]methanone (410 mg) described in Preparation Example 60, (R)-4-ethyloxazolidin-2-one (138 mg) described in Preparation Example 26, potassium carbonate (276 mg) and copper (I) iodide (38 mg) were added toluene (1.5 mL) and N,N′-dimethylethylenediamine (43 μL), and the mixture was refluxed for 2.5 hr. Since the starting materials were left, copper (I) iodide (38 mg) and N,N′-dimethylethylenediamine (43 μL) were added and the mixture was further refluxed for 2 hr. The reaction mixture was cooled, ethyl acetate and aqueous ammonium chloride solution were added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a 1:1 mixture of saturated aqueous ammonium chloride solution and ammonia water, and the mixture was washed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium chloride solution, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography (chloroform:methanol) to give the title compound (279 mg).

후처리

  1. temperaturethe mixture was refluxed for 2.5 hr
  2. waitSince the starting materials were left
  3. temperaturethe mixture was further refluxed for 2 hr
  4. temperatureThe reaction mixture was cooled
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with a 1:1 mixture of saturated aqueous ammonium chloride solution and ammonia water
  7. washthe mixture was washed once with saturated aqueous ammonium chloride solution, once with saturated aqueous sodium chloride solution
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customThe residue was purified by column chromatography (chloroform:methanol)

출처 및 근거

ORD 기록
ord-0f7d7a29118348219cb541f1405a1c41
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354401B2

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